Effectiveness of Chinese prescription Kangen-karyu for dyslipi-demia, using 3T3-L1 adipocytes and type 2 diabetic mice.

The Chinese prescription Kangen-karyu, comprised of six crude drugs, has received much attention due to its numerous biological activities. The present study was conducted to examine whether Kangen-karyu has an ameliorative effect on dyslipidemia. The effect of Kangen-karyu was evaluated using 3T3-L1 adipocytes, and also db/db mice as an experimental model for diabetic dyslipidemia. Kangen-karyu significantly inhibited adipocyte differentiation and lipid accumulation. Kangen-karyu also down-regulated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ, sterol regulatory element-binding protein (SREBP)-1c, and fatty acid synthase, and the protein levels of aP2 and PPARγ, which indicates that Kangen-karyu inhibited adipogenesis during adipocyte differentiation, and may have potential anti-dyslipidemia effects. In addition, the administration of Kangen-karyu reduced hyperlipidemia in db/db type 2 diabetic mice through a decline in the serum levels of lipids, and an improvement of lipoprotein profiles. The enhanced hepatic triglyceride level of the db/db mice was significantly reduced by Kangen-karyu administration through the down-regulation of SREBP-1 and lipogenic enzymes in the liver. These findings indicate that Kangen-karyu exerts anti-dyslipidemia effects in adipocytes and type 2 diabetic db/db mice.

Daily hydroxyl radical scavenging capacity of mammals.

Both the formation and reactions of hydroxyl radical (•OH) are quantitative chemical reactions even in mammalians, and so we can reproduce such in vivo reactions in test tubes. Daily urinary excretions of some reaction products have been used to estimate the amount of •OH produced daily. Although urinary 8-hydroxydeoxyguanosine (8-OHdG) is a well-known marker of •OH, we have shown that creatol (CTL: 5-hydroxycreatinine), an •OH adduct of creatinine (Crn), and its metabolite, methylguanidine (MG), are better markers, because the amount of •OH scavenged by deoxyguanosine (dG) in the body is negligible. We measured CTL and MG together with Crn in 24-h urine, and calculated their molar sum, CTL + MG, providing a daily estimate of moles of •OH scavenged with Crn, and, from the molar ratio (CTL + MG)/Crn, we can calculate the percentage of Crn that was used to scavenge •OH. Healthy subjects and normal rats were indicated to use circa (ca.) 0.2 and 0.3% of Crn in order to scavenge •OH, respectively, because the corresponding ratios, scavenged •OH/Crn, were 2.2 and 3.0 mmole/mole (24-h urine) (Crn scavenged ca. 20-25 µmole and ca. 200 pmole of •OH in healthy subjects and normal rats, respectively). Since 8-OHdG/Crn has been reported to be 1.9 µmole/mole (24-h urine), the daily scavenging capacity with Crn is 10(3)-fold more than dG. In patients with chronic renal failure (CRF) or chronic kidney disease (CKD) at stages 3-5: glomerular filtration rate (GFR) < 60 mL/min/1.73 m(2), •OH levels increased in proportion to the severity of CKD: up to ca. 3% of Crn was used daily in order to scavenge •OH. Although the accumulation of MG in organs has not been reported except for the brain and skin tissues in normal animals, •OH increases markedly and MG becomes detectable in all organs such as the kidney, liver, and heart in CRF rats.